复发性卵巢上皮癌干细胞标志物BCRP与相关因子的表达及其临床意义

Clinical significance and expression of cancer stem cells marker BCRP in recurrent epithelial ovarian cancer.

目的:探讨肿瘤干细胞标志物及相关因子在复发性卵巢上皮性癌中的表达及意义。方法:免疫组化检测30例同一位卵巢癌患者初治与复发时手术切除的配对组织标本中干细胞标志物乳腺癌耐药蛋白(BCRP)及相关因子、P糖-蛋白(P-gp)、肺耐药蛋白(LRP)、蛋白激酶B(PKB/Akt)的表达,结合临床病理及随访资料进行分析。结果:(1)BCRP过度表达与卵巢癌复发明显相关(P<0.05),而P-gp、LRP和Akt过度表达与卵巢癌复发无显著相关性(P>0.05);(2)与初发癌相比,复发卵巢癌低分化癌构成比显著上升(P<0.05);(3)BCRP的表达与患者病理分级显著相关(P<0.05),而P-gp、LRP、和Akt与患者病理分级无关(P>0.05);(4)BCRP、P-gp、LRP和Akt表达阴性患者化疗反应率明显高于表达阳性的患者(P<0.05);(5)在复发卵巢癌组织中BCRP与P-gp、LRP、Akt表达均呈正相关关系(rs=1.0,P<0.01)。结论:BCRP表达与卵巢癌复发、获得性耐药显著相关,与卵巢癌的失分化程度亦密切相关,提示肿瘤干细胞持续存在与增长可能是导致卵巢癌复发的主要原因。

Objective：To explore the biological significance of expression of cancer stem cells marker in recurrent epithelial ovarian cancer（EOC）. Methods：By using immunohis- tochemisty,cancer stem cells maker breast cancer resistant protein（ BCRP）, P-glycoprotein （P- gp）, lung resistance protein （LRP）, protein kinase B （PKB/Akt）were analyzed in 30 paired tissue samples taken from primary and recurrent patients with EOC. The clinical pathological and monitoring data were combined to examine the significance of these markers. Results： The overexpression ratios of P-gp, LRP and Akt in recurrent tissues showed no significant difference compaired with those in the primary tissues（P〉0.05）. The overexpression ratio of BCRP in recurrent cancer tissues was significantly higher than that in primary tissues （P〈0.05）. The reviewed clinicopathological data demonstrated that the recurrent course of ovarian cancer had significant relationship with the transformation of histological differentiation of tumor from high to low（ P〈0.05）. BCRP was significantly associated with the pathologic differentiation of ovari-an cancer tissues（P〈0.05）. However, P-gp, LRP and Akt had no significant relation with the pathologic differentiation of ovarian cancer（P〉0.05）. In the recurrent EOC, the chemothera- peutic reaction rate in patients with the negative BCRP, P-gp, LRP and Akt was significantly higher than that in patients with the positive BCRP, P-gp, LRP and Akt （P〈0.05）. The expression of BCRP had positive correlation with expression of P-gp, LRP and Akt in the recurrent EOC（rs=1.0, P〈0.01 ）. Conclusion： BCRP is significantly correlated with recurrence, acquired multidrug resistance and low-grade differentiation in EOC. These results suggest that cancer stem cell may play an important role in the recurrence and acquired multidrug resistance in EOC.